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TrpA1 regulates thermal nociception in Drosophila

Abstract

Pain is a significant medical concern and represents a major unmet clinical need. The ability to perceive tissue-damaging stimuli is required for an animal's survival and, thus, the process is under strict evolutionary pressure. We have developed a high throughput behavioral system to identify genes that contribute to thermal nociception in the fruit fly and reported a large-scale screen that identified the Ca2+ channel straightjacket (stj) as a conserved regulator of thermal nociception. Here we present the minimal anatomical and neuronal requirements for Drosophila to avoid noxious heat in our novel behavioral paradigm. Bioinformatics analysis of our whole genome data set revealed 23 genes implicated in Ca2+ signaling that are required for noxious heat avoidance. One of these genes, the conserved thermoreceptor TrpA1, was confirmed as a bona fide "pain" gene in both adult and larval fly nociception paradigms. The nociceptive function of TrpA1 required expression within the Drosophila nervous system, specifically within nociceptive multi-dentritic (MD) sensory neurons. Our analysis identifies the channel TRPA1 as a conserved regulator of nociception.